September 2003

Everyone is somewhere on the Neurodevelopmental Spectrum. Where are you on it .... where do you want to be?

Accelerated neurodevelopment allows us the ability to maximize and use our intellectual, physical, and emotional strengths simultaneously, no matter where we begin on the spectrum.

When accelerating brain power, daily tasks such as working, studying, and sports become easier to do and manage. The brain is functioning at optimal levels and is able to make quick attentional shifts on demand.

This is the state of mind that peak performers call "the zone" and is accessible at will.

Approach to Nutritional and Health Supplements Spells Trouble for Consumers, Says Project: FANS WASHINGTON, Aug 13, 2003 (U.S. Newswire via COMTEX) -- Following is a statement of Project: Freedom of Access to Nutritional Supplements on the Dietary Supplement Safety Act of 2003: "Instead of the Senate adding yet another new law to the books, creating more government bureaucracy, and increasing American's tax burden as a result, they should fully enforce the current law," stated Beth Clay, director of Project: FANS. "To do that properly we need to fully fund DSHEA, not replace it with a new law (S.722) that could kill the entire industry and remove nearly all vitamins and supplements from the market. "If S.722 becomes law, seven out of 10 consumers could lose access to nutrition supplements and important dietary aids necessary for their health and well-being," continued Clay. The new bill, known as the Dietary Supplement Safety Act of 2003, was introduced by Senator Dick Durbin (D-Ill.), and co-sponsored by Sens. Hillary Clinton (D-N.Y.), Dianne Feinstein (D-Calif.) and Chuck Schumer (D-N.Y.). According to MS. Clay, "the impact of this law on consumers and the nutrition supplement industry would be as damaging as Hillarycare would have been on our health care system. Durbin's proposed new law would install a system more complex and costly than the current $800 million process required of the prescription drug industry." The current law of the land is the Dietary Supplement Health and Education Act of 1994 (DSHEA), which was made into law by a strong bi-partisan effort. It gives the FDA all the tools they need to properly regulate the supplement industry. DSHEA has never been properly funded since it was passed in 1994. Congressional focus should be on properly funding DSHEA, not replacing it. "American consumers need to know their freedoms are about to be limited. If S.722 becomes law it will affect everyone; from five-year-old children who take chewable vitamins, to those who rely on iron supplements, to women who use calcium to help prevent osteoporosis," concluded Clay. "...Seven out of 10 consumers could lose access to nutrition supplements and important dietary aids necessary for their health and well-being." -- Beth Clay, Project: FANS WHAT IS A "CHEMICAL IMBALANCE"? McGill Mental Health The term " chemical imbalance" is thrown around a lot these days. True conditions caused by chemical imbalances are relatively rare. All thoughts, feelings and motions in the brain are mediated by the release of chemicals in brain pathways. Every persons brain is unique, leading each of us to have different traits and abilities. Just because your brain works in a particular way, does not mean that you have a chemical imbalance. A certain amout of sadness, anxiety or other emotional upset is normal, and though we may be able to block these feelings by chemicals, this would tend to de-humanize us. Even when we use medication to help an individual with overwhelming emotions, most of the time this is not to repair a "chemical imbalance" but simply to help contain symptoms. The newer anti-depressants, known mostly as SSRIs can have a mood dampening effect, in that they seem to contain intense emotions in many individuals. The usefullness of this aspect has to be considered in light of a person's whole life.   ANTI-DEPRESSANT MEDICATION: CURRANT STATE OF KNOWLEDGE Over the past ten years there has been an explosion in the development and the use of new anti-depressant drugs.  Last year SSRI's were prescribed to 20% of the adult population in Canada.  These medications are being marketed for an ever increasing list of indications.  However the efficacy of these drugs as the primary treatment for many of these disorders is still questionable.  This is especially true in the use of anti-depressant medication in adolescents and young adults, where research has shown overall poor responses to this class of drugs.  The following points are of crucial importance in evaluating the use of medication in the student population. Research on brain development have indicated that in the post-natal to adolescent period, an overabundance of receptor sites are produced in many brain pathways.  These sites are pruned during the late adolescent and early adult period.  This implies that artificially increasing neurotransmitter levels during this period could potentially lead to an overpruning of receptor sites.  It is therefore possible that prescribing anti-depressant medication to people aged 18-24 could make them prone to depressions throughout their adult life.  With our present state of knowledge, we have no assurance that the use of psychotropic medication in young people does not have adverse long term effects. SSRI's do not just effect serotonin pathways.  Most of these drugs effect noradrenaline and dopamine pathways, especially at higher doses.  Research on depression in adolescents has consistently shown that anti-depressant medication has no advantage over placebo.  There has been no research done specifically on a young adult population.  Clinical experience indicates that these populations are similar. Research on treatment of depression by medication in adult populations have consistently shown that medications seem effective primarily in Major Depression with Melancholia.  Other depressive syndromes show only marginal responses to medication when compared to placebos. Major Depression with Melancholia is a rare diagnosis in young adults.  Most depressions in young adults show a labile mood pattern.  However this may not be evident on an initial interview. Side effects experienced by a student population tend to be more pronounced then described in the literature.  This is probably due to increased expectations and the active lifestyle of students. Recommendations: The use of anti-depressant medication in the student population needs to be very carefully considered.  While these medications may be valuable in certain conditions, the possible ramifications of treatment, both physiological and psychological can be profound.  Anti-depressant medication should rarely be prescribed on a first visit.  It is impossible to make an accurate assessment of consistent symptoms in students without at least two in-depth interviews.  Medication should not be considered to be a primary treatment modality in students.  Most students respond well to therapy without the need for medication. OTHER MEDICATIONS There are many mdications used in psychiatry that are useful for various symptoms. Most of these are best for short term use as an adjunct to therapy. Some more severe conditions may require long term use of medication, but these conditions need to be properly diagnosed by an expert.           Review for child neurologists on the topic of Attention Deficit Hyperactivity Disorder (ADHD). Brain and Development, 2003 The purpose of this review is to give child neurologists an update on the topic of Attention Deficit Hyperactivity Disorder (ADHD). Because child neurologists are often consulted about whether or not a child has the syndrome of Attention Deficit Hyperactivity Disorder (ADHD), the fact that their colleagues in psychiatry have taken the lead in naming the syndrome and developing criteria for the diagnosis means that the child neurologist has to go to the pages of the Diagnostic and Statistical Manual IV [1] in order to answer the question, ''Does this child have combined/full, primarily inattentive, or primarily hyperactive/impulsive type Attention Deficit Hyperactivity Disorder (ADHD)?'' The child neurologist can go beyond the formality of adhering to the diagnosis set forth in the DSM-IV [1] and add to that some of the specifics of confirmatory diagnosis; this is because there are so many comorbidities and confounds (producing pseudoADHD) that the real value added by the child neurologist is to reframe the question. Beyond simply establishing whether the child meets criteria for ADHD as a diagnosis, the child neurologist can provide empirical evidence for the child's status neurobiologically, characterizing what is implied by the diagnosis and explaining that there is some brain basis to the phenomenon.

Effects of delayed administration of a green tea polyphenol on the changes in polyamine levels and neuronal damage after transient forebrain ischemia in gerbils So-Young Lee, Choong-Young Kim, Jung-Jeung Lee, Jung-Gil Jung and Seong-Ryong Lee Brain Research Bulletin, 2003 Abstract (-)-Epigallocatechin gallate has a potent antioxidant property and can reduce free radical-induced lipid peroxidation as a green tea polyphenol. In previous study, systemic administration of (-)-epigallocatechin gallate immediately after ischemia has been shown to inhibit the hippocampal neuronal damage in the gerbil model of global ischemia. Polyamines are thought to be important in the generation of brain edema and neuronal cell damage associated with various types of excitatory neurotoxicity. We examined the effects of delayed administration of (-)-epigallocatechin gallate on the changes in polyamine levels and neuronal damage after transient global ischemia in gerbils. To produce transient global ischemia, both common carotid arteries were occluded for 3 min with micro-clips. The gerbils were treated with (-)-epigallocatechin gallate (50 mg/kg, i.p.) at 1 or 3 h after ischemia. The polyamines; putrescine, spermidine, and spermine levels were examined using high performance liquid chromatography in the cerebral cortex and hippocampus 24 h after ischemia. Putrescine levels in the cerebral cortex and hippocampus were increased significantly after ischemia and the delayed administrations of (-)-epigallocatechin gallate (1 or 3 h after ischemia) attenuated the increases. Only minor changes were noted in the spermidine and spermine levels after ischemia. In histology, neuronal injuries in the hippocampal CA1 regions were evaluated quantitatively 5 days after ischemia. (-)-Epigallocatechin gallate administered 1 h or 3 h after ischemia significantly reduced hippocampal neuronal damage. The present results show that the delayed administrations of (-)-epigallocatechin gallate inhibit the transient global ischemia-induced increase of putrescine levels in the cerebral cortex and hippocampus. (-)-Epigallocatechin gallate is neuroprotective against neuronal damage even when administered up to 3 h after global ischemia. These findings suggest that (-)-epigallocatechin gallate may be promising in the acute treatment of stroke. Bipolar disorder link found A dramatic increase in the number of Australians suffering from what was formerly known as manic depression has been linked to dietary changes over the last decade. In particular, the finger is being pointed at a reduction in Omega-3 fatty acids - most commonly found in oily fish and usually linked to a reduced risk of cardiovascular disease. Sydney psychiatrist Gordon Parker, who heads the NSW Black Dog Institute for research into depression, said bipolar disorder was long thought to affect one per cent of the population. However recent studies in the US and Scandinavia had documented a tenfold increase. The latest figures indicated as many as one in ten now suffered from the disorder, with the increase particularly marked among those with the milder variant known as bipolar 2. Unlike bipolar 1, people with bipolar 2 did not suffer delusions or hallucinations, and for this reason they often slipped through the net, Prof Parker said. However they still experienced the characteristic pattern of extreme mood swings, alternating between highs and lows. The condition - once believed never to occur before adolescence - was now being diagnosed in children as young as three in some parts of the US. Australia seemed to be mirroring those trends, Prof Parker said. "We at the institute are also seeing the signs of a dramatic increase in bipolar 2 in this country, but one that has not yet reached community and professional awareness," he said. Prof Parker's comments were based on observations that 20 per cent of patients attending the depression clinic at the Prince of Wales Hospital; 30 per cent of those using the telepsychiatry service and almost half of referrals to his outpatient practice were suffering from bipolar disorder. The increase in bipolar remained a mystery, although there were several theories, he said. These included an increase in caffeine consumption, greater use of illicit drugs, better diagnosis or simply the increasingly unsustainable pace of modern life. However the most likely explanation was a "change in the natural history of the disorder itself" - either through genetic changes or environmental changes, including diet. "The dramatic increase over the last decade remains unexplained," he said. "A strong possibility and one we're pursuing is actually a dietary factor." That factor, Prof Parker believes, is a reduction in consumption of Omega-3 fatty acids. He said it was known that Omega-3 played a role in minimising the risk of cardiovascular disorders as well as directly affecting the brain and helping people with depressive disorders who did not respond to conventional treatment. "The possibility that, as our diet has changed and we've taken away the Omega-3, that this may be determining (the increase in bipolar disorder) is at least a testable hypothesis," he said. Dr Parker said his group had recently begun research to test the theory using postnatal women and measuring the levels of fatty acids in the blood of people with depressive and cardiac disorders. Increasing Use of Stimulants and Antidepressants In Children Sounds an Alarm By Ellen Kuwana Neuroscience for Kids Staff Writer In the past few years, drugs such as Prozac (an antidepressant) and Ritalin (a stimulant used to treat Attention Deficit Hyperactivity Disorder [ADHD]) have become household names. These drugs ease a variety of symptoms and have been approved for use by people six years of age and older. Because of the dramatic behavioral and generally beneficial changes that Prozac and Ritalin can bring about, these drugs are commonly prescribed and used to treat mood disorders. However, an alarming trend has surfaced in which these medications are being routinely prescribed and administered to very young children between two and four years old. In a study published in the February 23, 2000 issue of the Journal of the American Medical Association, researchers found found that the use of antidepressants and stimulants in children two to four years old had doubled, and in some cases tripled, between 1991 and 1995 in the US. These findings seriously trouble many child health and development professionals. Study Raises Red Flags First and foremost, there have been no long-term studies examining the effects of these drugs on children under the age of six. Children's brains and adults' brains respond very differently to some medications. There have been no research studies that examine how these drugs work in very young children. On the other hand, there have been several studies that suggest these drugs cause changes in the brains of young animals. For example, drugs (such as Prozac) that affect the reuptake of the neurotransmitter serotonin, appear to decrease the number of synapses in the developing rat cortex. Young rats exposed to these drugs developed memory problems that persisted into adulthood. During development, neurons in the brain make many connections, and drugs may affect how these connections are made. The number of synapses in the cortex is greatest at about the age of three in humans, and then selective elimination ("pruning") occurs, as other connections strengthen over the following years. How these drugs affect the developing brain is not currently known. They could alter how neurons are generated or "born," how neurons migrate to the proper places in the brain, how axons grow, or how synapses form. Because of these unknowns, the label on Ritalin warns against using this drug in children under the age of six. Second, the widespread use of these drugs highlights a problem in the health care system: limited health care professionals. It is estimated that there are seven to 12 million children in the US with some form of mental illness, yet there are only 5,500 child psychiatrists in the US. This number of child psychiatrists is not adequate. Many children with psychiatric problems see doctors who do not specialize in behavioral issues and are not fully trained to diagnose or treat these disorders. Many of these disorders, such as ADHD, cannot be diagnosed with certainty at these young ages. A third concern is that prescribing a pill has become a "quick fix." Many doctors may not try less invasive treatments, such as behavioral interventions. This situation is further complicated by insurance issues, which often limit the number and/or type of doctor visits that are covered. Perhaps this is like having a car with an engine that is not working properly. Instead of taking it to a mechanic to get the problem diagnosed and fixed, the owner buys a loud car stereo instead, to cover up the engine noise. Although this works for a time, it is only a short-term solution, and does not work on the main problem. Furthermore, the loud music may be damaging the owner's ears! What is Being Done to Address these Concerns The public needs more information about how Ritalin and Prozac affect children under the age of six. The recent study is limited in scope because it is a cross-sectional study, meaning it looked at medication use in children at one point in time. A long-term study is needed to see how long the children were on the medications, and how it affected their brain development. The National Institute of Mental Health is planning a $6 million, five-year study on the use of Ritalin in children under the age of six. References: 1. Children and Medications - reports from the National Institute of Mental Health 2. Okie, S., More tots are given Prozac, Ritalin; researchers troubled by increasing use, Seattle Times, February 23, 2000. 3. American Academy of Child and Adolescent Psychiatry 4. Magno Zito, J, Safer, D.J., dosReis, S., Gardner, J.F., Boles, M., Lynch, F., Trends in the prescribing of psychotropic medications to preschoolers, JAMA, Vol. 283 No. 8, February 23, 2000. 5. Coyle, J.T., Psychotropic drug use in very young children, JAMA, February 23, 2000, pp. 1059-1060. Surface visualization of electromagnetic brain activity Alexandra Badea, George K. Kostopoulos and Andreas A. Ioannides Journal of Neuroscience Methods, 2003, 127:2:137 - 147 Abstract Advances in hardware and software have made possible the reconstruction of brain activity from non-invasive electrophysiological measurements over a large part of the brain. The appreciation of the information content in the data is enhanced when relevant anatomical detail is also available for visualization. Different neuroscientific questions give rise to different requirements for optimal superposition of structure and function. Most available software deal with scalar measures of activity, especially hemodynamic changes. In contrast, the electrophysiological observables are generated by electrical activity, which depends on the synchrony of neuronal assemblies and the geometry of the local cortical surface. We describe methods for segmentation and visualization of spatio-temporal brain activity, which allow the interplay of geometry and scalar as well as vector properties of the current density directly in the representations. The utility of these methods is demonstrated through displays of tomographic reconstructions of early sensory processing in the somatosensory and visual modality extracted from magnetoencephalography (MEG) data. The activation course characteristic to a specific area could be observed as current density or statistical maps independently and/or contrasted to the activity in other areas or the whole brain. MEG and functional magnetic resonance imaging (fMRI) activations were simultaneously visualized. Integrating and visualizing complementary functional data into a single environment helps evaluating analysis and understanding structure/function relationships in normal and diseased brain.

ALZHEIMER'S RESEARCH

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Enzyme may protect against Alzheimer's Nature Science Update July 2003 HELEN R. PILCHER A protein called Pin1 may prevent degenerative brain disorders from developing. When it is removed, ageing mice develop symptoms similar to those of Alzheimer's disease, a new study reveals1. Future human therapies may seek to boost Pin1 levels. Pin1 is an enzyme. In the test tube, it hastens the untangling of clumps of a spaghetti-like protein called tau that build up inside sickly, ageing nerve cells. "By increasing Pin1 function in degenerating neurons, we might be able to protect the brain from Alzheimer's disease," says Kun Ping Lu of Harvard Medical School in Boston, who led the study. Alzheimer's disease affects more than four million people in the United States alone. Nearly half of those over 85 years old are affected. Tau tangles are also found in the brains of people with other forms of dementia and with Down's syndrome. Anti-Alzheimer's drugs currently in development either seek to prevent proteins from becoming tangled, or to unravel them once they have become jumbled. Pin1 boosters may prove to be a useful addition to this pharmaceutical toolkit, says Alzheimer's researcher Brian Anderton of King's College London. Pin1 is normally found in the healthy human brain, although its function remains elusive. Lu and colleagues decided to see what happens when it is absent. Mice lacking the Pin1 gene develop protein tangles in their brain and spinal cord as they age, and their nerve cells die off. "We don't know if their memory is impaired," says Lu. Other researchers are less sure about the enzyme's link to Alzheimer's disease. Mice lacking Pin1 develop tau tangles, but they do not have amyloid plaques - deposits of a different protein that form around nerve cells in Alzheimer's patients. It's difficult to ascribe function to a protein by looking at the lack of it, warns Thomas Arendt, who works on Pin1 at the University of Leipzig in Germany. All available animal models of Alzheimer's disease mimic only a subset of its symptoms. The Pin1-deficient mouse may be more natural than existing models engineered to overproduce abnormal proteins, suggests Anderton. Lu's strain is the first to develop a degenerative brain disease due to a protein being removed. "When you overexpress something, there are all sorts of things that you're not controlling," he says. Pin head Lu's team also analysed the brains of ten Alzheimer's patients. Healthy cells had high levels of Pin1; ailing cells, replete with tangles, had little of the protein. This hints that the enzyme may also protect healthy regions of the demented human brain, suggests Lu. "It's difficult to ascribe function to a protein by looking at the lack of it." Thomas Arendt University of Leipzig The research may even help to bridge a divide that has long existed in the Alzheimer's research community. Scientists tend to focus on either tangles or plaques, explains Bart de Strooper of the Catholic University of Leuven, Belgium. "The big question is how are amyloid and tangles related at the chemical level," he says. Pin1 may be the missing link, he speculates. To find out, researchers plan to cross Pin1-deficient mice with other 'high-tangle' or 'high-plaque' strains. They will then assess the degree and type of degeneration produced to see how Pin1, plaques and tangles interact.

PREEMIE NEWS

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Perinatal exposure to aluminum alters neuronal nitric oxide synthase expression in the frontal cortex of rat offspring Kisok Kim Brain Research Bulletin, 2003 Abstract Disturbance of the neuronal nitric oxide signaling pathway by chronic exposure to aluminum (Al) in drinking water may be a causal factor of neurological disorders in offspring. In order to investigate the relationship between Al administration and expression of neuronal nitric oxide synthase (nNOS), the numbers and distribution patterns of nNOS-immunoreactive neurons were examined in the frontal cortex of offspring after exposure to 0, 5, and 10 mM of Al in drinking water during prenatal and neonatal periods. At the bregma 0.20 level, the number of nNOS-positive neurons was significantly increased (10%) and decreased (17%) following exposure to 5 and 10 mM of Al in drinking water, respectively. The change was more severe in the upper layer than in deep layer of the cortex. In contrast, at the bregma -2.80 level, the number and distribution pattern was not significantly changed following exposure to Al. These data suggest that Al toxicity may be mediated through disturbances to the nitric oxide signaling pathway and exhibits a biphasic effect, especially in the frontal area of the cortex. In addition, the results suggest that impaired expression of nNOS plays an important role in the development of neurological syndrome caused by an exposure to Al during the early developmental stage. What is periventricular leukomalacia (PVL)? "Peri" means near; "ventricular" refers to the ventricles or fluid spaces of the brain, "leukomalacia" is softening of the white matter of the brain. Periventricular leukomalacia is softening of the brain near the ventricles. The softening occurs because brain tissue in this area has died. Why do premature babies get PVL? PVL is thought to be due to too little blood flow to that part of the brain either when the baby is a fetus in the womb, at delivery, or after delivery during the first days of life. Usually doctors do not know exactly when this occurred. How will my doctors know if my baby has PVL? Most often the baby has no signs or symptoms. PVL is diagnosed by a test called a cranial (head) ultrasound. It is a painless test, performed at the bedside, in which sound waves are used to give a picture of the baby's brain. Because PVL usually takes a few weeks to become detectable, babies at risk for PVL are tested 4 to 8 weeks after birth. Sometimes this test will first show a suspicious area which may or may not turn out to be PVL. With serial tests it will become more clear. How is PVL treated? There is no specific treatment for PVL. Can my baby have both IVH (intraventricular hemorrhage) and PVL? Yes, it is common for babies who have grade III or IV IVH to also have areas of PVL. What are the complications of PVL? Because PVL results from loss of brain tissue, babies with PVL are at very high risk for abnormal development later on. The more severe the PVL, the more likely a baby will develop mental or motor (movement) problems. Even babies who just had suspicious areas need to have their development followed closely. How do I know if my baby will be abnormal because of PVL? This can be determined only over time. Near the time of discharge, the baby may be less responsive to his/her environment or to peoples' faces than babies without PVL. Serious abnormalities appear gradually. These may include: * motor (movement) problems - legs often worse than arms: * tight or stiff muscles * holding legs straight and crossed most of the time * difficulty sitting * slow to crawl, stand, or walk or inability to do these * abnormal crawling, toe walking * frequent arching of the back (not just when angry or at play) * slow mental development * does not listen to your voice by age 3-4 months after hospital discharge * does not make different sounds by 8-9 months after discharge * doesn't seem to understand or say any words by one year after discharge * seizures - not common * poor hearing or deafness * poor vision Less serious problems appear more slowly, are more difficult to detect, and may not be obvious until preschool or grade school. These can include: * poor coordination or balance * specific learning disabilities (math or reading) * very short attention span * behavioral problems * difficulty with activities that require coordination of the eyes and hands; for example, catching a ball or copying a simple drawing It is very important for babies who have PVL to receive close follow-up of their development. If your baby has PVL, s/he may be eligible for a developmental intervention program. Anytime in the future if you are concerned about something that you think might be abnormal, have it checked out by your baby's doctor. In vivo quantitative ultrasonic evaluation of neonatal brain with a real time integrated backscatter imaging system Chizu Fujimoto, Yushiro Yamashita, Hiroshi Kanda, Eimei Harada, Yasuki Maeno and Toyojiro Matsuishi Brain and Development, 2003 Abstract We applied the integrated backscatter (IBS) imaging system to the evaluation of the normal neonatal brain of different birth-weights: extremely low-birth-weight (N=13), very-low-birth-weight (N=14), low-birth weight (N=14), and normal birth weight (N=19). The IBS values in six regions of interest, the deep white matter, subcortical white matter, choroid plexus, thalamus, lateral ventricle, and occipital bone, were compared among groups of different birth weights, gestational age, and postnatal age: at the date of birth and 28~30 days after birth. The IBS values were higher in the order of bone>choroid plexus>deep white matter>subcortical white matter>thalamus>lateral ventricle and were significantly different except for the lateral ventricle in all the groups at days 0 and 28~30. The IBS values increased with the decrease of birth weight and gestational age. There was a decrease of IBS values at day 28 compared to that of day 0 in the extremely low birth weight and very low birth weight groups; however, they remained the same in infants with low birth weights and in the normal birth weight group. Further studies to evaluate the significance of this technique for the objective diagnosis of brain insults in neonates are necessary. Amplitude spectral analysis of maturational changes of delta waves in preterm infants Akihisa Okumura, Tetsuo Kubota, Naoko Toyota, Hiroyuki Kidokoro, Koichi Maruyama, Toru Kato, Fumio Hayakawa and Kazuyoshi Watanabe Brain and Development, 2003 Abstract The aim of this study is to clarify the usefulness of amplitude spectral analysis for an evaluation of maturational changes of delta activities in preterm infants. We chose each ten healthy infants without complications who were 29–30, 31–32, and 33–34 weeks of post-conceptional age (PCA) at electroencephalogram (EEG) recordings. Fast Fourier transform algorithm was applied for amplitude spectral analysis. The analyzed data were divided into four frequency bands; D1 0.53–1, D2 1–2, D3 2–3, and D4 3–4 Hz. The average amplitude of six segments with high voltage slow waves was calculated in each frequency band. A significant reduction of the amplitude along with PCA was present in all leads in D1 band. On the other hand, a significant negative correlation with PCA was observed only in the occipital leads in D2, D3 or D4 bands. In conclusion, maturational EEG changes assessed by amplitude spectral analysis were prominent in the occipital areas, and in the frequency less than 1 Hz.

BRAIN PLASTICITY

Brain Plasticity: What Is It? Learning and Memory NeuroScience For Kid University of Washington Brain Plasticity--An Overview What is brain plasticity? Does it mean that our brains are made of plastic? Of course not. Plasticity, or neuroplasticity, is the lifelong ability of the brain to reorganize neural pathways based on new experiences. As we learn, we acquire new knowledge and skills through instruction or experience. In order to learn or memorize a fact or skill, there must be persistent functional changes in the brain that represent the new knowledge. The ability of the brain to change with learning is what is known as neuroplasticity. To illustrate the concept of plasticity, imagine the film of a camera. Pretend that the film represents your brain. Now imagine using the camera to take a picture of a tree. When a picture is taken, the film is exposed to new information -- that of the image of a tree. In order for the image to be retained, the film must react to the light and “change” to record the image of the tree. Similarly, in order for new knowledge to be retained in memory, changes in the brain representing the new knowledge must occur. To illustrate plasticity in another way, imagine making an impression of a coin in a lump of clay. In order for the impression of the coin to appear in the clay, changes must occur in the clay -- the shape of the clay changes as the coin is pressed into the clay. Similarly, the neural circuitry in the brain must reorganize in response to experience or sensory stimulation. Facts About Neuroplasticity FACT 1: Neuroplasticity includes several different processes that take place throughout a lifetime. Neuroplasticity does not consist of a single type of morphological change, but rather includes several different processes that occur throughout an individual’s lifetime. Many types of brain cells are involved in neuroplasticity, including neurons, glia, and vascular cells. FACT 2: Neuroplasticity has a clear age-dependent determinant. Although plasticity occurs over an individual’s lifetime, different types of plasticity dominate during certain periods of one’s life and are less prevalent during other periods. FACT 3: Neuroplasticity occurs in the brain under two primary conditions: 1. During normal brain development when the immature brain first begins to process sensory information through adulthood (developmental plasticity and plasticity of learning and memory). 2. As an adaptive mechanism to compensate for lost function and/or to maximize remaining functions in the event of brain injury. FACT 4: The environment plays a key role in influencing plasticity. In addition to genetic factors, the brain is shaped by the characteristics of a person's environment and by the actions of that same person. Developmental Plasticity: Synaptic Pruning Gopnick et al. (1999) describe neurons as growing telephone wires that communicate with one another. Following birth, the brain of a newborn is flooded with information from the baby’s sense organs. This sensory information must somehow make it back to the brain where it can be processed. To do so, nerve cells must make connections with one another, transmitting the impulses to the brain. Continuing with the telephone wire analogy, like the basic telephone trunk lines strung between cities, the newborn’s genes instruct the "pathway" to the correct area of the brain from a particular nerve cell. For example, nerve cells in the retina of the eye send impulses to the primary visual area in the occipital lobe of the brain and not to the area of language production (Wernicke’s area) in the left posterior temporal lobe. The basic trunk lines have been established, but the specific connections from one house to another require additional signals. Over the first few years of life, the brain grows rapidly. As each neuron matures, it sends out multiple branches (axons, which send information out, and dendrites, which take in information), increasing the number of synaptic contacts and laying the specific connections from house to house, or in the case of the brain, from neuron to neuron. At birth, each neuron in the cerebral cortex has approximately 2,500 synapses. By the time an infant is two or three years old, the number of synapses is approximately 15,000 synapses per neuron (Gopnick, et al., 1999). This amount is about twice that of the average adult brain. As we age, old connections are deleted through a process called synaptic pruning. Synaptic pruning eliminates weaker synaptic contacts while stronger connections are kept and strengthened. Experience determines which connections will be strengthened and which will be pruned; connections that have been activated most frequently are preserved. Neurons must have a purpose to survive. Without a purpose, neurons die through a process called apoptosis in which neurons that do not receive or transmit information become damaged and die. Ineffective or weak connections are "pruned" in much the same way a gardener would prune a tree or bush, giving the plant the desired shape. It is plasticity that enables the process of developing and pruning connections, allowing the brain to adapt itself to its environment. Plasticity of Learning and Memory It was once believed that as we aged, the brain’s networks became fixed. In the past two decades, however, an enormous amount of research has revealed that the brain never stops changing and adjusting. Learning, as defined by Tortora and Grabowski (1996), is “the ability to acquire new knowledge or skills through instruction or experience. Memory is the process by which that knowledge is retained over time.” The capacity of the brain to change with learning is plasticity. So how does the brain change with learning? According to Durbach (2000), there appear to be at least two types of modifications that occur in the brain with learning: 1. A change in the internal structure of the neurons, the most notable being in the area of synapses. 2. An increase in the number of synapses between neurons. Initially, newly learned data is "stored" in short-term memory, which is a temporary ability to recall a few pieces of information. Some evidence supports the concept that short-term memory depends upon electrical and chemical events in the brain as opposed to structural changes such as the formation of new synapses. One theory of short-term memory states that memories may be caused by “reverberating” neuronal circuits -- that is, an incoming nerve impulse stimulates the first neuron which stimulates the second, and so on, with branches from the second neuron synapsing with the first. After a period of time, information may be moved into a more permanent type of memory, long-term memory, which is the result of anatomical or biochemical changes that occur in the brain (Tortora and Grabowski, 1996). Injury-induced Plasticity: Plasticity and Brain Repair During brain repair following injury, plastic changes are geared towards maximizing function in spite of the damaged brain. In studies involving rats in which one area of the brain was damaged, brain cells surrounding the damaged area underwent changes in their function and shape that allowed them to take on the functions of the damaged cells. Although this phenomenon has not been widely studied in humans, data indicate that similar (though less effective) changes occur in human brains following injury. For references and more information on neuroplasticity, see: 1. Drubach, D. (2000). The Brain Explained, Upper Saddle River, NJ: Prentice-Hall, Inc. 2. Gopnic, A., Meltzoff, A., Kuhl, P. (1999). The Scientist in the Crib: What Early Learning Tells Us About the Mind, New York, NY: HarperCollins Publishers. 3. John F. Kennedy Center for Research on Human Development, Vanderbilt University Staff. Brain Plasticity, Retrieved July 28, 2002 from http://www.vanderbilt.edu/kennedy/topics/brainpl.html 4. Kandel, E.R., Schwartz, J.H., and Jessell, T.M. (2001). Principles of Neural Science. (4th ed.), New York: McGraw-Hill. 5. Kolb, B. (Winter 2000). Experience and the developing brain. Education Canada, 39(4), 24-26. 6. Neville, H.J. and Bavelier, D. (2000). Specificity and plasticity in neurocognitive development in humans. In Gazzaniga, M.S. (Ed). The New Cognitive Neurosciences. (2nd ed.), Cambridge, MA: The MIT Press, pp. 83-99. 7. Society for Neuroscience. (July 2000). Brain Plasticity, Language Processing and Reading, Retrieved August 3, 2002 from http://apu.sfn.org/content/Publications/BrainBriefings/brain_lang_reading.html 8. Sousa, D.A. (2001). How the Brain Learns (2nd ed.), Thousand Oaks, CA: Corwin Press, Inc. 9. Tortora, G. and Grabowski, S. (1996). Principles of Anatomy and Physiology. (8th ed.), New York: HarperCollins College Publishers. 10. Tulving, E. and Craik, F.I.M. (Eds.) (2000). The Oxford Handbook of Memory, London and New York: Oxford University Press. Controlling the critical period of plasticity Takao K. Hensch May 2003; Abstract Neuronal circuits are shaped by experience during 'critical periods' of early postnatal life. The ability to control the timing, duration, and closure of these heightened levels of brain plasticity has recently become experimentally possible. Two seemingly opposed views of critical period mechanism have emerged: (1) plasticity may be functionally accessed throughout life by appropriately modified stimulation protocols, or (2) plasticity is rigidly limited to early postnatal life by structural modifications. This overview synthesizes both perspectives across a variety of brain regions and species. A deeper understanding of critical periods will form the basis for novel international efforts to ''nurture the brain''.

NEUROTRANSMITTER NEWS

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Creatine 'Boosts Brain Power' The dietary supplement creatine - known to improve athletic performance - can also boost memory and intelligence, researchers claim. Creatine is a natural compound found in muscle tissue, and has been popular with athletes looking for ways to increase fitness. However, experts say that it has a role in maintaining energy levels to the brain, and have the theory that taking more creatine might actually improve mental performance. Researchers from the University of Sydney and Macquarie University, also in Australia, tested this by giving creatine supplements to 45 young adult volunteers. Vegetarians were used for the tests, mainly because meat in the diet is in itself a source of creatine, and it would be difficult to gauge exactly how much an individual had consumed. The volunteers were split up and given either creatine or a "dummy" pill for periods of six weeks. The researchers, led by Dr Caroline Rae found that the creatine supplements - at least in the short term - seemed to suggest a positive effect. Developmental pharmacodynamics: implications for child and adolescent psychopharmacology Normand Carrey, MD; Stan Kutcher, MD J Psychiatry Neurosci 1998;23(5):274ú6 Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia © Canadian Medical Association Developmental pharmacodynamics is the study of neurofunctional capabilities, how these develop during the life span and how this development affects responses to psychotropic agents. It is well recognized that various neuroanatomical regions and neurotransmitter systems develop at different rates and mature at different times. 1 Our understanding of these developments is derived from studies that have investigated neurotransmitters, receptors, second messengers, glial cells, hormones and nerve trophic factors; this growing body of knowledge is integral to our improved understanding and treatment of child and adolescent psychiatric disorders. This commentary will limit itself to the role 2 neurotransmitters, serotonin (5-HT) and dopamine, and their receptors, play in development. The serotonergic system provides an excellent example of how the interplay of neurotransmitters, receptors and glial cells reciprocally affects development. 5-HT was described as a potential "developmental signal" by Lauder as early as 19832 when he postulated that 5-HT played a different role in the immature brain than in the mature one. Prenatal depletion of 5-HT with p-chlorophenylalanine (PCPA) delays the onset of neurogenesis in 5-HT target regions,3 whereas 5-HT stimulation with 5-methoxytryptamine produces dose-dependent effects on neurite outgrowth.4 5-HT can thus be conceptualized as playing a dual role in development: autoregulation of the serotonergic neurons themselves and development of target tissues.5 Another example of the teratogenic effects on developing neural fields induced by blocking 5-HT involves feeding pregnant mother rats ethanol, resulting in a significant decrease in 5-HT innervation of the cortex and brain stem of their pups. This effect can be prevented by pretreatment with buspirone.6 Serotonergic neuroreceptors acquire different developmental functions as the organism matures; there are regional and receptor subtype specificities, the functions of which change during maturation. Serotonergic receptors in rats attain peak levels in fetal or early postnatal life and then decrease to adult levels.7 For some receptor subtypes, the highest number of receptors occurs during brain development when properly functioning synapses are not yet present. The 5-HT1C receptor may play a role in the regulation of cell division whereas the 5-HT1A type may regulate differentiation. During development, the 5-HT1A receptor is transiently expressed in high numbers and is often expressed in regions from which it is absent in the adult brain.8 The 5-HT1A receptor subtype has been thought to play a critical role in both neuronal and glial cell growth through trophic effects of nerve growth factors. Whitaker-Azmitia and Azmitia9 have shown that astroglial cells promote immature neuron growth through the secretion of S-100, a nerve growth factor, but the effect is mediated through 5-HT1A receptors on brain astroglial cells. As serotonergic neurons mature, the level of S-100 decreases, as does the number of 5-HT1A receptors on astroglia. Drugs that act as agonists to the 5-HT1A receptor, such as 8-hydroxy-di-propylaminotetralin (8-OH-DPAT), promote astroglial cell maturity. Studies of rodents have demonstrated the functional effects of these developmental changes. Teicher and Baldessarini1 observed that acute administration of imipramine to the adult rat produces sedation, whereas this is not shown until 4 weeks of age in the younger rat due to the delayed development of a serotonin-mediated inhibitory response. Similarly, McCracken and Poland10 found that in prepubertal rats the prolactin response to a serotonin agonist was not enhanced by pretreatment with amitriptyline, whereas in adult rats the prolactin response was enhanced. They suggested that immature organisms may lack the full capacity to upregulate a 5-HT-receptor-coupled response. These ontogenetic differences in the development of this monoamine system may help explain the documented differences in clinical response to antidepressants and placebo in studies comparing children and adolescents to adults. A similar developmentally sensitive role has also been documented for the dopamine receptor. The highest numbers of both D1 and D2 receptors occur in the immature brain in rats, baboons and humans.7 D2 receptors are transiently expressed in the frontal cortex of the immature rat but are absent in the adult brain. Dopamine receptors, like neuronal cell number, synapses and dendritic processes, undergo pruning as part of the developmental process. However, if receptors are blocked neonatally or are deprived of stimulation, permanent changes in binding or compensatory receptor expression may occur in adults, such as is demonstrated when neonates are treated with neuroleptics or are lesioned with 6-hydroxydopamine.11 Additionally, the D1 receptor has been localized on growth cones, the tips of the growing nerve terminal, suggesting a role in influencing neuronal differentiation and maturation. In rodent models, animals exposed to neuroleptics demonstrate developmentally specific differences in behavioural expression. For example, before rats are weaned (21 days and younger), they are very sensitive to the motor (bradykinetic) and sedative effects of neuroleptics, whereas periadolescent rats (28 to 38 days) display very strong cataleptic reactions. This parallels children's susceptibility to extrapyramidal side effects of dopamine blockade. The incidence of drug-induced dystonias and bradykinetic reactions diminishes strikingly with maturation from ages 10 to 19 years to adulthood,12 whereas neuroleptic-induced akathisia is less common in children. Neuroleptic-withdrawal dyskinesias are more common in children.13 This simplistic overview belies the complexity not only of each neurotransmitter system, but also of the multiple interactions possible between these systems during development. One neurotransmitter may have multiple effects on different systems during development. Liu and Lauder14 have shown that 5-HT, through regional effects on either raphe glia or mesencephalic glia, promote nerve growth factors affecting the maturity of serotonergic neurons or tyrosine hydroxylase neurons, respectively. Alternatively, D1 receptors have been shown to inhibit growth cone motility in serotonergic terminals; for example, if rat pups are treated prenatally with a D1 agonist, they will have greatly reduced serotonin uptake sites as adults. Knowledge of neuroreceptor development has profound implications for our understanding of child and adolescent psychiatric disorders and the possible salutary or deleterious effect of psychotropics on brain development. For example, Andersen and colleagues15 have shown that D1 and D2 receptors are first overproduced and then pruned to a greater extent in the striatum of male rats than of female rats. Dopamine receptors reach their peak at day 40 and then decrease dramatically by day 60, the period of time corresponding to puberty in the rat. From this observation, Andersen and her group have speculated that the onset, gender disparity and adolescent alterations in the clinical picture that occur in attention-deficit/hyperactivity disorder and Tourette's syndrome may stem from disregulation of receptor density development. They also found a profound reduction in 5-HT turnover in the nucleus accumbens during the peripubertal period. Again, they propose that the disinhibition, aggression and mood lability of adolescence may be due to alterations in serotonergic transmission. Many of the long-term effects of psychotropics on human developmental pharmacodynamics are not known. Based on animal data, which have shown that the blockade of neurotransmitters in the developing brain may result in a permanent downregulation of that receptor system, Vitiello and Jensen16 speculated that even a temporary blockade could result in a permanently underdeveloped system. In contrast, if psychotropic compounds can arrest the degeneration of specific brain functioning postulated to underlie such illnesses as schizophrenia, these treatments may have preventive effects. As child and adolescent psychiatrists stride toward earlier identification of childhood depression, psychosis, anxiety and obsessive-compulsive disorders, the intuitive logic of prescribing to children psychotropic drugs known to be effective in adults without knowledge of their relation to neurodevelopment should be tempered by careful clinical research. This research should be based on "bottom up" rather than "top down" strategies, in which the development of psychopharmacologic interventions is informed by an understanding of the ontogeny of the central nervous system. References 1. Teicher M, Baldessarini R. Developmental pharmacodynamics. In: Popper C, editor. Psychiatric pharmacosciences of children and adolescents. Washington (DC): American Psychiatric Press; 1987. 2. Lauder J, Wallace J, Wilkie M, Dinome A, Krebs H. Roles for serotonin in neurogenesis. Monog Neural Sci 1983;9:3-10. 3. Lauder J, Krebs H. Effects of p-chlorophenylalanine on time of neuronal origin during embryogenesis in the rat. Brain Res 1976;107:638-44. 4. Shemer, Azmitia E, Whitaker-Azmitia P. Dose-related effects of prenatal 5-methoxytryptamine (5-MT) on development of serotonin terminal density and bahavior. Dev Brain Res 1991;59:59-63. 5. Whitaker-Azmitia P, Druse M, Walker P, Lauder J. Serotonin as a developmental signal. Behav Brain Res 1996;73:19-29. 6. Tajuddin N, Druse M. Treatment of pregnant alcohol consuming rats with buspirone. Alcohol Clin Exp Res 1993;17:110-4. 7. Whitaker-Azmitia P. Role of serotonin and other neurotransmitter receptors in brain development: basis of developmental pharmacology. Pharmacol Rev 1991;43:553-61. 8. Borella A, Bindra M, Whitaker-Azmitia P. Role of 5-HT-1A receptor in the development of the neonatal rat brain: preliminary behavioral studies. Neuropharmacology 1997;36(4/5):445-50. 9. Whitaker-Azmitia P, Azmitia E. Astroglial 5-HT-1A receptors and S-100B in development and plasticity. Perspect Dev Neurobiol 1994;2(3):223-38. 10. McCracken J, Poland R. Reduced effect of antidepressant on prolactin response to a serotonin agonist in prepubertal rats. J Child Adolesc Psychopharmacol 1995;5(2):115-20. 11. Broaddus W, Bennett J. Postnatal development of striatal dopamine function. Dev Brain Res 1990;52:273-7. 12. Keepers G, Clappison V, Casey D. Initial anticholinergic prophylaxis for acute neuroleptic induced extrapyramidal syndromes. Arch Gen Psychiatry 1983;40:1113-7. 13. Campbell M, Adams P, Perry R, Spencer E, Overall J. Tardive and withdrawal dyskinesia in autistic children: A prospective study. Psychopharmacol Bull 1988;24:251-5. 14. Liu J, Lauder J. Serotonin promotes region-specific glial influences on cultured serotonin and dopamine neurons. Glia 1992;5:306-17. 15. Andersen SL, Rutstein M, Benzo JM, Hostetter JC, Teicher MH. Sex differences in dopamine receptor overproduction and elimination. Neuroreport 1997;8:1495-8. 16. Vitiello B, Jensen P. Developmental perspectives in pediatric psychopharmacology. Psychopharmacol Bull 1995;31:75-81.

AUTISM

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Purkinje cell vulnerability and autism: a possible etiological connection Janet Kinnear Kern Brain and Development, 2003, Abstract Autism is a neurological disorder of unknown etiology. The onset of the abnormal growth and development within the brain is also not known. Current thought by experts in autism is that the time of onset is prenatal, occurring prior to 30 weeks gestation. However, autism comprises a heterogeneous population in that parents report either that their child was abnormal from birth, or that their child was developmentally normal until sometime after birth, at which time the child began to regress or deteriorate. Anecdotal reports suggest that some children with autism have significant illness or clinical events prior to the development of autistic symptoms. Conceivably, these children may become autistic from neuronal cell death or brain damage sometime after birth as result of insult. To support this theory is that marked Purkinje cell loss, the most consistent finding in the autistic disorder, can result from insult. Evidence suggests that the Purkinje cell is selectively vulnerable. This article discusses a theory that the selective vulnerability of the Purkinje cell may play a role in the etiology of autism, and suggests that a future direction in autism research may be to investigate the possibility of neuronal cell loss from insult as a cause of autism. Results of a small pilot survey are also discussed.

EEG/ERP

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Evidence for the different additivity of the temporal and frontal generators of mismatch negativity: a human auditory event-related potential study Petri Paavilainen, Mikko Mikkonen, Markku Kilpeläinen, Reia Lehtinen, Miiamaaria Saarela and Lauri Tapola June 2003; Abstract The auditory sensory-memory mechanisms in the human brain were investigated using the mismatch negativity (MMN) component of the event-related potential. MMNs were recorded to stimuli deviating from the repetitive standard stimuli simultaneously either in one or two features (frequency, intensity). If the processing of these two features is independent of each other, the MMN to the double deviant should equal the sum of the MMNs elicited by the corresponding single deviants. The double-deviant MMNs were found to be additive at the electrode sites below the Sylvian fissure but not at the frontal scalp areas. The results suggest that the temporal subcomponent of MMN is additive whereas the frontal is non-additive. The pattern of results was similar in ignore and attend conditions, suggesting that the components were not attentionally modulated. Visual and auditory event related potentials in epileptic children: a comparison with normal and abnormal MRI findings Dilsad Turkdogan, Onder Us and Gulseren Akyuz Brain and Development, 2003, Abstract Visual and auditory event related potentials (VERPs and AERPs) in 32 epileptic children with magnetic resonance imaging (MRI) abnormalities and 18 with normal MRI were recorded and compared to the data of 21 healthy children. Of all 50 epileptic children (34 male, 16 female) aged 14.42±4.27 (7–20) years, 21 were medically intractable and receiving polytherapy. The mean latencies of N2 and P3 components of VERPs and AERPs in all epileptic children were significantly higher than those of the controls (P<0.05). Epileptic children with structural abnormalities had more prolonged latencies of N2 and P3 components of AERPs and VERPs than those of the healthy children (P<0.05). The epileptic children with normal MRI had significantly more prolonged latency of N2 and P3 of VERPs and P3 of AERPs than those of the controls (P<0.05). The difference of the mean latency of N2 and P3 components or the mean amplitude of P3 components of ERPs between the two epileptic groups was insignificant. The type of medication (mono- versus polytherapy) did not affect the wave components of ERPs. We suggest that epileptic activity, itself, leads to prolonged N2 and P3 components of AERPs and VERPs. The presence of structural abnormality indicated by imaging is not a predictor of ERPs abnormalities.

Free fatty acids in cerebrospinal fluids from patients with traumatic brain injury Julie G. Pilitsis, William M. Coplin, Michael H. O'Regan, Jody M. Wellwood, Fernando G. Diaz, Marilynn R. Fairfax, Daniel B. Michael and John W. Phillis June 2003; Abstract Free fatty acid (FFA) concentrations in cerebrospinal fluid (CSF) are recognized as markers of brain damage in animal studies. There is, however, relatively little information regarding FFA concentrations in human CSF in normal and pathological conditions. The present study examined FFA concentrations in CSF from 15 patients with traumatic brain injury (TBI) and compared the data with values obtained from 73 contemporary controls. Concentrations of specific FFAs from TBI patients, obtained within 48 h of the insult were significantly greater than those in the control group (arachidonic, docosahexaenoic and myristic, P<0.001; oleic, palmitic, P<0.01; linoleic, P<0.05). Higher concentrations of total polyunsaturated fatty acids (P<0.001) and of arachidonic, myristic and palmitic acids measured individually in CSF (P<0.01) obtained 1 week after the insult were associated with a worse outcome at the time of hospital discharge using the Glasgow Outcome Scale. This preliminary investigation suggests that CSF FFA concentrations may be useful as a predictive marker of outcome following TBI.

Chipping away at brain function: mining for insights with microarrays Gilbert L Henry, Karen Zito and Josh Dubnau (August 18, 2003), Abstract The impact of microarray studies on neurobiology has been limited because, with the exception of a few outstanding papers, most reports provide little more than lists of genes, often leaving the reader at a loss to understand which and how many of the identified transcripts will be true positives with significant biological impact. However, some recent papers have offered considerable biological insight by providing independent in vivo confirmation of the roles of candidate genes, offering a glimpse of the potential power of microarrays in neurobiological research. Increased cortical excitability induced by transcranial DC and peripheral nerve stimulation J. Uy and M.C. Ridding Journal of Neuroscience Methods, 2003, 127:2:193 - 197 Abstract This study investigated the effect of short periods of simultaneous weak anodal direct current (DC) stimulation and peripheral ulnar nerve (ES) stimulation on corticospinal excitability. The experiments involved repeated testing of ten normal subjects with four different protocols: (1) No Stimulation; (2) DC only; (3) ES only; (4) DC plus ES. Motor evoked potentials (MEP) were recorded from the First Dorsal Interosseous (FDI); Abductor Digiti Minimi (ADM) and Flexor Carpi Ulnaris (FCU). The baseline MEP amplitude was compared with that obtained immediately after the first set of stimulation, after the second set of stimulation, 15 min post stimulation and 30 min after stimulation. No significant change was seen with the No Stimulation and ES Only protocols. FDI showed a significant change in the DC protocol after the second set of stimulation but the changes were not present 15 or 30 min after. The DC plus ES protocol showed FDI changes that were significant after the second set of stimulation with the elevations persisting when tested 15 and 30 min post intervention. These observations show that a period of anodal DC stimulation preceding a period of ulnar nerve stimulation resulted in significant and persistent elevations in cortical excitability.

A temporal window for the central inhibition of stuttering via exogenous speech signals in adults Tim Saltuklaroglu, Joseph Kalinowski, Vikram N. Dayalu, Vijaya K. Guntupalli, Andrew Stuart and Michael P. Rastatter Neuroscience Letters, 2003 June 2003; Abstract We explored a possible temporal window for central stuttering inhibition via exogenously presented speech signals. Thirteen adults who stutter were asked to read while listening to a continuous vowel /a/, or a repeating 1 s vowel /a/ followed by 1, 3 and 5 s silences. In all conditions, stuttering was significantly reduced. However, the continuous and 1 s repeating conditions showed the greatest reduction in stuttering relative to all other conditions. Furthermore, these conditions did not differ significantly from each other, suggesting a temporal window of at least 1 s for stuttering inhibition induced by a 1 s stimulus. We propose that exogenous speech signals provide an additional speech source that engages mirror neurons for 'on-line' stuttering inhibition during continous speech. Employing dual speech sources results in 'on-line' stuttering inhibition and continuous speech flow. In contrast, endogenous (single source) inhibitory techniques require speech flow to be interrupted and go 'off-line' to derive the mirror neuronal.

The effects of enhanced visual feedback on human synchronization Tanja Ceux, Martinus J. Buekers and Gilles Montagne June 2003; Abstract The execution of actions not only reposes on the spatial and temporal organization of the movements as such but also on their appropriate imbedding into the environmental spatio-temporal constraints. Actually, performance outcome appears to be strongly influenced by the strength of the perception-action coupling. The present experiment wants to examine to what degree this coupling strength affects the spatial and spatio-temporal characteristics of a synchronization task. In particular, the effects of: (i) enhanced visual feedback; and (ii) a modification in the spatial organization of the task were investigated. To do so, a task was designed in which horizontal arm movements had to be synchronized with a target light moving horizontally or vertically at a sinusoidal speed. Subjects performed six experimental conditions representing three synchronization modes (horizontal in-phase, horizontal anti-phase and orthogonal) and two feedback conditions (no feedback and feedback). The results for movement amplitude and relative phase revealed the operation of task specific effects. Apparently, the availability of feedback at the perception-action coupling level provoked the use of different strategies to cope with the constraints of this synchronization task.

Secrets of China's ancient cure for malaria laid bare PARIS, Aug 20 (AFP) - Scientists believe they have unlocked the workings of an ancient Chinese herbal remedy which has become one of the brightest yet most puzzling hopes in the war against malaria. The knowledge, they hope, may give rise to a new generation of cheaper, more effective drugs against a scourge that kills around a million people each year and infects hundreds of millions more. "We are particularly pleased to have found the missing piece in the anti-malarial jigsaw and solved one of the longest-running mysteries about how a critical anti-malarial works," the researchers said in a statement on Wednesday, on the eve of the publication of their work. "We cannot wait to apply this information in areas where there is a lot of drug resistance in (malaria) parasites." The remarkable story behind the herb starts off in 340 AD, when a Taoist scribe wrote "Zhou Hou Bei Ji Feng" ("Handbook of Prescriptions for Emergency Treatments"), giving a recipe for using sweet wormwood (qing hao) in an infusion for treating fever. More than 1,200 years later, a Chinese sage, Li Shizen, realised that this could be used for tackling the symptoms of malaria, and included the treatment in a compendium that is a landmark in Chinese medical history. There things lay until 1972, when Chinese scientists took an interest in the plant's reputed qualities. They successfully extracted the plant's active compound, calling it qing hao su -- transcribed into artemisinin in conventional scientific terminology, after the herb's Latin name, Artemisia annua. Artemisinin has since become a leading medication against the malaria parasite, not least in Southeast Asia, where the cheapest frontline treatments, chloroquine and sulphadoxine-pyrimethamine, are encountering big resistance problems. But how artemisinin works has never been clear. The prevailing theory was that it interacts with haem molecules, the iron-rich debris from red bloodcells which are destroyed by the parasite as it replicates around the body. This interaction then unleashes massive quantities of free radicals -- atoms with unpaired electrons which are linked with cell death -- which go on to kill the parasite, according to this thinking. But years-long research led by Sanjeev Krishna of St. George's Hospital Medical School in London concludes that artemisinin takes a quite different path. Artemisinin, they found, works by blocking the action of a metabolic enzyme called PfATP6 that is vital for "pumping" calcium in and out of the parasite's cells. All complex cells need calcium "pumps" to drive their molecular motors. Krishna's team, which infected frogs' eggs with the enzyme and exposed them to artemisinin and a conventional rival, believe that PfATP6 is exclusive to the malaria bug as the activator of its "pump". If this is confirmed by more biochemical evidence, rather than by observation alone, that opens an exciting new target against the parasite and one that is far less prone to mutation, which is the source of drug resistance. And it also throws up the possibility of synthesising cheap drugs that, like a sniper's bullet, specifically shut down the parasite's calcium "pump" but have no effect on anything else in the body. "PfATP6 is... now a prospective target for the development of new antimalarial drugs," World Health Organisation (WHO) tropical disease expert Robert Ridley says. "(...) The ever-growing threat of resistance to antimalarial drugs gives the work of Krishna and colleagues a practical significance beyond its undoubted academic merit." The study and commentary are published on Thursday in Nature, the British science weekly.

Persistent activity in the prefrontal cortex during working memory Clayton E. Curtis and Mark D'Esposito August 18, 2003 Abstract The dorsolateral prefrontal cortex (DLPFC) plays a crucial role in working memory. Notably, persistent activity in the DLPFC is often observed during the retention interval of delayed response tasks. The code carried by the persistent activity remains unclear, however. We critically evaluate how well recent findings from functional magnetic resonance imaging studies are compatible with current models of the role of the DLFPC in working memory. These new findings suggest that the DLPFC aids in the maintenance of information by directing attention to internal representations of sensory stimuli and motor plans that are stored in more posterior regions. Neurobiology of Learning and Memory     Claudio Da Cunha, Samantha Wietzikoski, Evellyn C. Wietzikoski, Edmar Miyoshi, Marcelo M. Ferro, Janete A. Anselmo-Franci and Newton S. Canteras January 2003; Abstract The aim of the present study was to test if the nigrostriatal pathway is an essential component for a water maze cued task learning and if it works independently of the hippocampal memory system. This hypothesis was tested using an animal model of Parkinson's disease in which male Wistar rats were lesioned in the substantia nigra pars compacta (SNc) by the intranigral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), thus causing a partial depletion of striatal dopamine. SNc-lesioned and sham-operated animals were implanted bilaterally with guide cannulae above the dorsal hippocampus in order to be tested after the administration of 0.4 µl 2% lidocaine or saline into this structure. The animals were tested in a spatial or in a cued version of the water maze, memory tasks previously reported to model hippocampal-dependent spatial/relational and striatal-dependent S–R learning, respectively. Hippocampal inactivation, but not SNc lesion, impaired learning and memory in the spatial version of the water maze. An opposite situation was observed with the cued version. No significant interaction was observed between the SNc lesion and hippocampal inactivation conditions affecting scores in the spatial or in the cued version of the water maze. These results suggest that the nigrostriatal pathway is an essential part of the memory system that processes S–R learning and that it works independently of the hippocampal memory system that processes spatial/relational memories.

NUTRITIONAL NEWS

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Sub-Clinical Neurobehavioral Abnormalities Associated with Low Level of Mercury Exposure through Fish Consumption Plinio Carta, Costantino Flore, Rossella Alinovi, Antonio Ibba, Maria Giuseppina Tocco, Gabriella Aru, Roberta Carta, Emanuela Girei, Antonio Mutti, Roberto Lucchini and Francesco Sanna Randaccio Neurotoxicology, 2003, 24:4-5:617-623 Abstract In order to assess early neurotoxic effects associated with relatively low levels of mercury absorbed through fish eating, two groups of 22 adult male subjects, habitual consumers of tuna fish, and 22 controls were examined using a cross-sectional field study. The assessment included neurobehavioral tests of vigilance and psychomotor function, hand tremor measurements and serum prolactin assessment. Mercury in urine (U-Hg) and serum prolactin (sPRL) were measured in all exposed subjects and controls, whereas measurements of the organic component of mercury in blood (O-Hg) were available for only 10 exposed and six controls. U-Hg was significant higher among exposed subjects (median 6.5 µg/g of creatinine, range 1.8–21.5) than controls (median 1.5 µg/g of creatinine, range 0.5–5.3). The median values of O-Hg were 41.5 µg/l among the tuna fish eaters and 2.6 µg/l in the control group. Both U-Hg and O-Hg were significantly correlated with the quantity of fish consumed per week. Significant differences in sPRL were found between exposed (12.6 ng/ml) and controls (9.1 ng/ml). Individual sPRL were significantly correlated with both U-Hg and O-Hg levels. The neurobehavioral performance of subjects who consumed tuna fish regularly was significantly worse on color word reaction time, digit symbol reaction time and finger tapping speed (FT). After considering the education level and other covariates, the multiple stepwise regression analysis indicated that O-Hg concentration was most significantly associated with individual performance on these tests, accounting for about 65% of the variance in test scores.